Common RNA-dependent pathways for motor-neuron degeneration in Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS)

Neurodegenerative disorders are complex and devastating diseases for which there is currently no effective treatment. Among them, Motor Neuron Diseases (MNDs) like amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are lethal disorders that respectively affect adults or young children, leading to muscle degeneration and death. Although much has been learned about the underlying genetics, we still do not understand their pathology, limiting our ability to perform diagnosis, prognosis and treatment.
This project is a multi-disciplinary cross-disease analysis of molecular pathways related to ALS and SMA. It combines fundamental, pre-clinical and neuro-pathological approaches with computational modeling, with the aim of identifying common underlying pathological processes in these diseases, overcoming traditional clinical boundaries.

How will we investigate Motor Neuron Diseases?

Primary data will be obtained in Drosophila fruit fly models of the two diseases, focusing on three different disease associated genes and their impact on adult central nervous system function. Through a multilevel integrative analysis, we expect to identify common pathways altered in both ALS and SMA, which may represent novel targets for the treatment of motor neuron disorders.
The findings will be translated to the human organism by characterizing candidate genes in tissue samples derived from patients, with the goal of developing clinically relevant markers and therapeutic targets. These will also allow for reliable monitoring of ALS and SMA disease progression and the eventual development of biomarkers for early therapeutic intervention.

Why use fruit flies as a model for MND research?

Animal models are important for research because they allow scientists to study diseases within the context of a complex organism and perform experiments that cannot be done on human patients. However, the use of vertebrate animals generates important ethical and welfare concerns.
In this regard, the fruit fly Drosophila has emerged as an invaluable system for the study of human neurodegenerative diseases. Although there are obvious differences between humans and flies, many molecular and cellular processes are shared among them. In fact, in addition to a complex nervous system, the fruit fly has counterparts for all genes associated to human MNDs, with mutations leading to symptoms highly related to the corresponding disease in patients. In combination with our ability to genetically manipulate flies, this makes Drosophila an amazing model organism for the study of MNDs.

Computational and Systems Biology approaches: working towards the Medicine of the future

The healthy or diseased state of an organism can be viewed as an emergent property that arises from intricate interactions between molecules, cells, organs and systems. Such complexity cannot be fully understood through traditional reductionist approaches. This is particularly relevant for neurodegenerative diseases, where common mechanisms are thought to hide behind seemingly distinct and multifaceted pathologies. Computational and Systems Biology provide the tools to investigate biological complexity, taking advantage of the growing amount of biomedical data - for mutations, gene expression, genetic and protein interactions – which are being massively generated by current technologies. By merging computational and experimental approaches in the context of an interdisciplinary team with medical doctors, geneticists, cell and molecular biologists, and computational scientists, we can start thinking about neurodegenerative diseases in new and productive ways that can effectively help improve patient’s lives.


This is an EU Joint Programme in Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organisations under the aegis of JPND - www.jpnd.eu: France, Agence Nationale de la Recherche; Germany, Bundesministerium fur Bildung und Forschung (BMBF); Portugal, Fundação para a Ciência e a Tecnologia; Spain, Instituto de Salud Carlos III (ISCIII).